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Oral Contraceptives and Breast Cancer Risk

Department of Obstetrics and Gynecology, Division of Gynaecology and Gynaecologic Oncology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

To the Editor:

We read the article by Brohet et al¹ with interest. The authors address a concern that is common among women with BRCA1/2 mutations as well as among their doctors: Are exogenous estrogens and progestins hazardous for these women? Female BRCA1/2 mutation carriers have an elevated risk of ovarian as well as breast cancer. Brohet and colleagues performed a carrier cohort study to investigate whether the existing elevated risk is even higher for women with current or past use of oral contraceptives.

They conclude that there is no evidence that current use of oral contraceptives is associated with a risk higher than the pre-existing elevated risk of breast cancer. However, the authors are concerned about the duration of use of oral contraceptives before the first pregnancy. In their study, they found a gradually rising hazard ratio from never use, 1 to 3 years, 4 to 8 years, and more than 9 years use of oral contraceptives. It may appear logical to conclude that with increased duration of use, oral contraceptives result in a higher risk of breast cancer.

However, the authors do not address the role of a potential confounding factor that may have a large effect on the conclusions that can be drawn from the presented data: age at first pregnancy. Women who have used oral contraceptives for a long time before they conceive will have their first pregnancy at a later age than women who did not use oral contraceptives at all, or only for a few years. It is well known that late age at first pregnancy is a risk factor for breast cancer.² Data on age at first pregnancy are not presented, and, in our opinion, this is an omission. It cannot be ruled out that the effect of duration of use of oral contraceptives on the elevated breast cancer risk is in fact a result of the later age at first pregnancy. We hope that the authors can produce data on age at first pregnancy of this cohort and thus shed some light on this obscure issue.

Another remarkable result of the study is the fact that women who started to use oral contraceptives before 1975 have a lower risk of breast cancer than women who started after 1975. This is remarkable, as oral contraceptives in the old days contained a higher dose of estrogens and progestins than those of the second and third generations as used after 1975. Hence, users who started before 1975 were exposed to a considerably larger dose of exogenous estrogens and progestins than users after 1975. If exposure to more exogenous hormones would result in a higher breast cancer risk, how do the authors explain this apparently contradictory result?

We appreciate and share the concerns of the authors regarding the (duration of) exogenous estrogens and progestins in women who are BRCA1/2 mutations carriers. However, on the basis of the data presented in this study, we see no reason to change our guidelines for these women regarding the use of oral contraceptives.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Brohet RM, Goldgar DE, Easton DF, et al: Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: A report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group. J Clin Oncol 25:3831-3836, 2007[Abstract/Free Full Text]

2. de Waard F, Thijssen JH: Hormonal aspects in the causation of human breast cancer: Epidemiological hypotheses reviewed, with special reference to nutritional status and first pregnancy. J Steroid Biochem Mol Biol 97:451-458, 2005[CrossRef][Medline]

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